THE SCIENTIFIC DAYS OF THE NATIONAL INSTITUTE FOR INFECTIOUS DISEASES PROF.DR. MATEI BALŞ

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1 -13 TH EDITION OF- THE SCIENTIFIC DAYS OF THE NATIONAL INSTITUTE FOR INFECTIOUS DISEASES PROF.DR. MATEI BALŞ - ABSTRACT VOLUME - BUCHAREST, 8-10 NOVEMBER 2017 ISSN ISSN L

2 PRESIDENT OF THE CONFERENCE Prof. Dr. Adrian Streinu-Cercel SCIENTIFIC COMMITTEE Prof. Dr. Adrian Streinu-Cercel Prof. Dr. Vlad Ratziu Dr. Olivier Patey Prof. Dr. Victoria Aramă Dr. Mona Munteanu Prof. Dr. Monica Luminos Assoc. Prof. Dr. Elisabeta Benea Dr. Mariana Mărdărescu Prof. Dr. Alexandru Rafila Assoc. Prof. Dr. Anca Streinu-Cercel Assoc. Prof. Dr. Oana Săndulescu Lect. Dr. Ana Maria Tudor Lect. Dr. Mihai Săndulescu POSTERS & PRESENTATIONS EVALUATION COMMITTEE Prof. Dr. Egidia Miftode Assoc. Prof. Dr. Irina Dumitru Prof. Dr. Monica Luminos Assoc. Prof. Dr. Cristina Popescu ORGANIZING COMMITTEE Dr. Sorin Petrea Psih. Odette Chirilă Assoc. Prof. Dr. Oana Săndulescu Assoc. Prof. Dr. Anca Streinu-Cercel Jr. Raluca Cruceru Daniela Dobrescu Lect. Dr. Mihai Săndulescu Dr. Mihaela Rădulescu Lect. Dr. Cătălin Tilişcan Claudiu-Mihai Şchiopu

3 Oral presentations Wednesday, November 8 th 2017 Round table Present and future goals in improving sepsis management through interdisciplinary efforts in the Intensive Care Department (ICD) of the National Institute for Infectious Diseases Prof. Dr. Matei Balș Doina Iovanescu 1 *, Catalin Apostolescu 1, Cleo Nicoleta Rosculet 1, Elena Cosmina Andrei 1, Tudor Vladoiu 1, Catalin Macovei 1, Viorica Mitescu 1, Dalila Ana Domuncu 1, Catrinel Ciuca 1, Ana Maria Cardamisa 1, Bogdana Manu 1, Cornel Camburu 1, Cristina Olariu 1 *liviuiovanescu@yahoo.cm The purpose of this study is the continuous improvement of the rapid methods of etiological diagnosis in infectious diseases and the choice of appropriate treatment considering a multidisciplinary approach, in order to maximize the results concerning the septic patients admitted to the ICD. We have conducted a thorough analysis of the medical records of all the patients admitted to our department in the first two quarters of The dynamics of severe cases has increased compared to In the first two quarters of 2017, there have been nearly 500 patients admitted to the ICD, half of which had the diagnosis of sepsis. The severity of the clinical presentation has increased, due to the emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR) or pandrugresistant (PDR) bacteria in the setting of previous therapeutic failures, the lack of adequate treatment in other units and the presence of severe comorbidities. It could easily be noticed the higher frequency of some groups: elderly (patients over the age of 75 representing 30-33% of cases), those with hematologic malignancies, diabetics, patients enrolled in programs of chronic hemodialysis (35%). Another category that came to our attention was represented by patients with heart disease which presented with high fever (25%). Our study also revealed the importance of neurological pathology in young patients (extremely severe clinical presentations of viral or autoimmune encephalitis), which has also shown an increase, representing 7-8% of the total number of cases. Comments: In order to increase treatment efficiency and improve the patients outcome, immediate action is imperative for creating and sustaining a local multidisciplinary team with full medical responsibility. The infectious disease physician should have an important role in adapting the antimicrobial therapy according to the presumed etiology: bacterial, viral or fungal. We want to obtain more data concerning the doses and penetration of new antibacterial molecules. We want to obtain new proof concerning the control of organ dysfunctions, as well as the timing of using non-invasive ventilation versus invasive techniques (ECMO or Prolung). Use of heart rate surveillance in hypovolemic shock to differentiate hemodynamic disorders induced by septic shock (IMACOR), cytosorb hemodialysis methods and endotoxin filters or plasmapheresis and hepatic dialysis (MARS) have proved to be useful in obtaining the time required for a successful surgical approach. In the presence of a proper legislative framework and adequate budgets, there s hope concerning the optimization and maximization of clinical outcomes. Acknowledgements We thank SPCIN, laboratory and clinical staff. 3

4 Thursday, November 9 th 2017 Impact of late presentation in the treatment effectiveness for HIV-infected patients in the Republic of Moldova Pavel Micsanschi 1 *, Tiberiu Holban 1, Constantin Spinu 3, Ina Bîstrițchi 1, Angela Nagîț 2, Irina Cucerova 2, Elena Ghitu 2 *micsanschipavel@gmail.com 1 Toma Ciorbă Clinical Hospital for Infectious Diseases, Chișinău, Republic of Moldova 2 Hospital of Dermatovenerology and Communicable Diseases, Chișinău, Republic of Moldova 3 National Public Health Center, Republic of Moldova The antiretroviral treatment may reduce morbidity and mortality at HIV-infected patients if it is initiated earlier before advanced stage of immunodeficiency and opportunistic infections has developed. Late presentation at the time of HIV diagnosis is mean as a association with clinical AIDS or/and CD4 count < 350cells/µL. The late presentation has not only a serious impact of HIV transmission but also had become a major threat in the efficacy of treatment and the deaths in AIDS. In this study was included 562 patients who corresponded late presentation criteria and was initiated the antiretroviral treatment in Included patients were aged between years (37.4±0.3 years), 51.96% (282 patients) were men. All the 562 patients who were confirmed with late presentation with the average CD4 cell count cells/µl were initiated the antiretroviral therapy. At the initiation of ART, all the patient included in this study were detected with CD4 counts <350 cells/µl, out of which 283 patients (50.35%) were detected with CD4 counts <200 cells/µl and 104 patients (18.5%) of them were detected with CD4 counts <50 cells/µl that is associated with increased risk for infections, morbidity and death. The most commonly used HAART regimens were TDF+FTC+EFV, TDF+3TC+EFV, (ABC+3TC) +EFV, (ABC+3TC) +LPV/r, (AZT+3TC) +EFV, (AZT+3TC) +LPV/r, AZT+3TC+NVP, (TDF+3TC) +AZT, (TDF+3TC) +LPV/r, (TDF+FTC) +LPV/r, (TDF+FTC) +NVP, DRV/r+(TDF+3TC). After initiation of antiretroviral therapy, 70 patients (12.45%) abandoned the therapy, 12 from them abandoned the therapy until twelve months, and 47 patients who had CD4 counts < 50cells/µL (8.36%) have died. Our study outcomes support the need for early identification of HIV infection that presents an opportunity to encourage safer behavior, which in turn improves the chance of treatment. Delayed diagnosis of HIV infection can lead in the late initiation of antiretroviral therapy, which subsequently could undermine the effectiveness of clinical and laboratory outcomes. Neurological impairment in children due to late detection of HIV Rodica Ungurianu 1 *, Mariana Mărdărescu 1, Alina Cibea 1, Magda Vasile 1, Dan Oțelea 1, Carmen Crăciun 1, Tatiana Colțan 1, Bianca Borcos 1, Betty Acs 2 *rodica.ungurianu@yahoo.com 2 National Institute for Mother and Child s Health Alessandrescu-Rusescu, Bucharest, Romania The number of HIV vertical transmission cases in Romania has continued to decrease since the early 2000s when the peak of the rate was 45%, to fewer than 2% at the end of As the national mother to child transmission protocol establishes, perinatally HIV exposed newborns undergo a specific assessment during the first 72 hours of life. Late detected cases with implicitly deferred introduction of specific therapy associate severe opportunistic infections and neurological impairment. We present the case of a pediatric male patient, late detected with perinatally acquired HIV infection in January 2015, at the age of 18 months, following several admissions in pediatric clinics, for intercurrent conditions. The HIV staging during his hospitalization on the Pediatric and Adolescents Immunodepression Department was symptomatic HIV infection, stage 3. Following the establishment of his diagnosis, we initiated the specific antiretroviral treatment based on the recommendations of the National Antiretroviral Treatment Guidelines. Eighteen months after his diagnosis the child presented: relatively rapid neurological impairment, drowsiness, intense headache, mobility and talk impairment, facial asymmetry. The head MRI evidenced two types of lesions: acute/active lesions with perilesional edema and other subacute/chronic lesions with no 4

5 post-contrast changes, all located in the white matter. The diagnosis of HIV infection-associated diseases indicated either progressive multifocal leukoencephalopathy a commonly associated illness or acute disseminated encephalomyelitis. The patients evolution was relatively favorable, due to a new antiretroviral therapeutic scheme, with strict monitoring of ART adherence, followed by complications difficult to manage at this age: hypertension, heart failure, hyperlactatemia. Late detection of perinatally acquired HIV in children imposes a standard protocol that includes imagistic screening transfontanellar ultrasound, CT/MRI, in order to rapidly identify neurological impairment and introduce a potent antiretroviral regime. parents for publication of this and any accompanying images. Cardiac disease in infants perinatally exposed to HIV infection and the associated risk factors Elena Tanase 1 *, Mariana Mardarescu 1, Rodica Ungurianu 1, Cristina Petre 1, Alina Cibea 1, Carina Matei 1, Cristi Anghelina 1, Ileana Leu 1, Dan Otelea 1, Tatiana Coltan 1, Bianca Borcos 1, Andreea Georgiana Birca 1, Ioana Alina Anca 2, Betty Acs 2, Alexandra Mardarescu 1 *tanaseelena4@gmail.com 2 National Institute for Mother and Child s Health Alessandrescu-Rusescu, Bucharest, Romania Cardiac disease is a frequent problem in children perinatally exposed to HIV infection. We analyzed the prevalence of cardiac birth defects in children born to HIV-infected women and factors that could be involved in it. Retrospective analysis of cardiac affections and the associated risk factors in infants exposed perinatally to HIV infection between 2015 and June 2017 evaluated in the National Institute for Infectious Diseases "Prof. Dr. Matei Bals", Bucharest. Of the 209 infants perinatally exposed to HIV infection 71 (33.97%) had cardiac abnormalities, of which 37 (17.7%) congenital malformations, most frequently single DSA or in association with other malformations and 34 (16.27%) arrhythmias, heart failure or systolic murmur. A total of 42 (20%) children were also exposed to HBV and HCV. Overall 20 (9.5%) of the infants with heart disease were born from drug-using mothers OR: 4.19, 95% CI: [ ], p= Mother s multiple ARV therapies and co-infection with HBV and HCV, as well as drug use, may represent risk factors for infants exposed perinatally to HIV infection. Additional studies are required. Ante- and postnatal monitoring of welfare dependent women and the risk of HIV transmission in their newborns. Data from the National Institute of Infectious Diseases Prof. Dr. Matei Bals, Alina Cibea 1 *, Marina Popov 1, Mariana Mărdărescu 1, Carina Matei 1, Cristina Petre 1, Rodica Ungurianu 1, Ruxandra Drăghicenoiu 1, Cristian Anghelina 1 *a_cibea@yahoo.com A particular category of children perinatally exposed to HIV in Romania is represented by cases of welfare dependency. These newborns come from low-income families, from unemployed mothers who are not married or don t have a stable partner, or who take drugs. We have analyzed the medical records and files of children perinatally exposed to HIV registered with the Welfare Services and hospitalized at the National Institute of Infectious Diseases Prof. Dr. Matei Bals in the period January 2013 October We assessed the parameters related to the families of these children, the medical and social status of mothers and children, and the number of hospitalization days and related costs. From a total of 825 children perinatally exposed to HIV during the above mentioned period, 61 (7.4%) are cases of welfare dependency. All these children come from poor families, 92% with a single parent (mothers who are not married, don t have a stable partner or have several partners); 65.5% are mother without education and 36% (22) iv drug addicts. 13% (8/61) of the children exposed from these have been HIV infected. 70% (43/61) of the welfare dependent cases resulted in child abandonment; these children have been placed in institutions or with foster mothers. They required 5

6 22 to 272 hospitalization days for various health issues or until their situation was settled. The perinatal transmission rate of HIV infection in welfare dependent mothers is about 3 times higher than the global transmission rate. This can be explained by a decreased adherence to medical care, lack of funds, poor education and drug consumption. The high level of child abandonment may lead to serious psycho-social issues of these children in the future. Prolonged hospitalization increases both the risk of intercurrent infections in these patients and the cost of medical care. The transmission way and cart regimens in HIV patients from the Cluj county between Corina Itu-Muresan 1 *, Cristian Jianu 1, Roxana Iubu 1, Cristian Marcu 1, Mihai Calin 1, Irina Filipescu 2, Adriana Topan 2 *corinaitu@yahoo.com 1 Clinical Hospital of Infectious Diseases, Cluj- Napoca, Romania 2 Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania Knowing the HIV transmission way is an important step in prevention strategies besides immediate initiation of ART. The European guidelines strategies regarding the third drug of cart have been changed during the time. In were NNRTIs, PIs and INSTIs. In 2015 the order of pharmacological classes changed, the first being INSTIs and then NNRTIs and PIs. We compared the year 2012 with 2016 regarding the transmission and cart regimens. We studied the confirmation sheets and medical recorders of patients beneficiaries of cart in 2012 and in We recorded demographic features and the third drug in cart for the first, the second, the third and more than three regimens. Associations were considered more than 2 pharmaceutical classes. We used Fisher s exact test, with statistic signification under The number of presentations was 110 patients in 2012 and 226 in In 2012 were 61 males and in 2016 were 167. In 2012 were 83 sexual transmission and 199 in Vertical transmission and Romanian cohort were the same. For 2012 and 2016 the first regiment with: NNRTIs: 17 and 43; with PIs: 21 and 40; with INSTIs: 0 and 13.The second with NNRTIs: 8 and 19; with PIs: 21 and 32; with INSTIs: 0 and 10.The third with NNRTIs: 6 and 5; with PIs: 7 and 18; with INSTIs: 1 and 8. More than three: with NNRTIs: 4 and 6; with PIs: 17 and 22; with INSTIs: 1 and 10; associations: 5 and 3. There were statistic significations: increased number of males, p=0.0001; increased sexual transmissions, p=0.004; increased in MSM, p=0.01; decreased number of more than three regiments in 2016, p=0.04; increased number of patients with INSTIs in 2016, p= and increased number of patients with darunavir/r, p=0.003 in Sexual way remains the main transmission, with increased MSM patients. Using INSTIs and PIs with high genetic barrier to resistance in 2016, the result was a decreased number of patients with more than three regimens in Former children, present-day adults Romanian cohort in Mureș county Lucia Carmen Chiriac 1,*, Nina Bodnar 1, Iringo Zaharia Kezdi 1, Andrea Incze 1, Cristina Gîrbovan 1, Cristina Manasturean 2, Anca Georgescu 1 *carmen.l.chiriac@gmail.com 1 Department of Infectious Diseases, University of Medicine and Pharmacy Tîrgu-Mureș, Romania 2 County Clinical Hospital Mureș, Tîrgu-Mureș, Romania During the 90s, Mureș county has also faced the HIV phenomenon. At that time, 376 cases of HIV infection (F1 clade) in children were registered, all infected by parenteral route of transmission. In 1995 the first antiretroviral treatment (ARVT) was initiated. We analyzed the present situation of the Romanian cohort in Mureș county from clinical, immunologic and virologic point of view. Out of all 229 HIVinfected patients under surveillance in Mureș county, 120 (52.40%) belong to the Romanian cohort. Median age of the cohort patients was 27 years % patients are female, 48.33% male. Therapeutic experience includes an average of 3.95 ARV drug regimens, minimum 1, maximum 15 regimens, corresponding to the prolonged history of HIV infection mean years since diagnosis % patients are co-infected with hepatitis B virus, 2.5% with hepatitis C virus. 9 (7.5%) patients developed pulmonary / extrapulmonary tuberculosis. 60% patients have 6

7 CD4 T-cells above 350 cells/μl and 52.2% have undetectable HIV-RNA plasma viral load. 30 children were born to patients belonging to the Romanian cohort, out of which we registered 1 case of mother-to-child transmission of HIV; 52% patients have optimum adherence to ARVT and a good quality of life. The evolution of HIV infection is less aggressive among patients from the Romanian cohort. Antiretroviral therapy initiated during the first years of life had a major role in increasing their life-span. Importance of antenatal HIV screening. A case study Bianca Borcos 1 *, Mariana Mardarescu 1, Rodica Ungurianu 1, Andreea Georgiana Birca 1, Florin Murgoci 2, Dan Otelea 1, Tatiana Coltan 1, Cristian Anghelina 1, Ileana Leu 1, Carina Matei 1, Alexandra Mardarescu 1 *bianca.bizera26@gmail.com Dr. Matei Bals, Bucharest, Romania 2 Marius Nasta Pneumoftiziology Institute, Bucharest, Romania HIV/AIDS infection still represents a public health issue in Romania, the first semester of 2017 registering 303 new HIV/AIDA cases (National HIV/AIDS Data Base) of which 5 cases in children between 0-14 years, through mother-to-child transmission. We assessed and established the HIV status of a 9 months old infant who arrived at the Immunodepression Department for Children and Adolescents in National Institute for Infectious Diseases Prof. Dr. Matei Bals in June 2017, following several admissions in different pediatric clinics in the country, for intercurrent respiratory infections and failure to thrive. Upon admission, the data from prior investigations, diagnostics and anamnesis revealed that the patient is the first child of a nineteen years old woman, with unmonitored pregnancy for HIV, HCV, HBV or STIs. The tests performed during the previous episodes of hospitalization raised successively suspicions of systemic inflammatory disease, possible sepsis, malignancy, possible viral infection on the underlying condition of systemic inflammation. The evaluations carried out in our clinic, including a first HIV test, displayed HIV infection in all three members of the family. The case required multidisciplinary approach and a prolonged hospital stay (more than two months), triggered by numberless complications due to the late detection of HIV. Also, an essential factor for the extended admission was progressive adherence to ART and specific cares on behalf of both parents. Although Romania has screening protocols for pregnant women, new cases of perinatally acquired HIV are still discovered. Most of the times the child is the first to be diagnosed followed by the parents testing who turn out to be HIV positive. Hence, an active involvement of both the family doctor and the community for an easier access of pregnant women to medical services would be necessary and beneficial. parents for publication of this and any accompanying images. Post-exposure prophylaxis for potentially contaminated biological products at the National Institute of Infectious Diseases Matei Balș, Bucharest Șerban Benea 1,2, Liana Gavriliu 1,2, Daniela Camburu 1, Alina Cozma 1, Gina Ducu 1, Roxana Dumitriu 1, Mihaela Ionica 1, Manuela Podani 1, Ramona Zamfir 1, Elisabeta Otilia Benea 1,2 * *oebenea@yahoo.com 2 Carol Davila University of Medicine and To prevent the transmission of HIV infection to the Matei Balș Institute, a local prophylaxis guide is used for professional and non-professional exposure to potentially contaminated biological products (since 2015). The recommendations of this guide correspond to the international recommendations in the field. We set out to look at the most important aspects of post-exposure prophylaxis in our institute in the first 6 months of Retrospective analysis of the cases presented at the Matei Balș Institute between 1 st of January and 30 th of June 2017 for accidental, professional or unprofessional exposure to potentially HIV contaminated biologic products that have received antiretroviral prophylaxis according to the local guidelines. 7

8 During the analyzed period there were 126 persons who received prophylaxis with antiretrovirals. The mean age was 32.9 years (7-79 years). Most subjects who received post exposure prophylaxis belonged to the age group (35.7%; 45/126 cases), followed by those in the age group years (30.2%; 38/126 cases), the group years (22.2%; 28/126 cases), newborns (7.9%; 10/126 cases), those aged over 60 (2.4%; 3/126 cases) and under 20 (1.6%; 2/126 cases). The gender distribution was 60.3% women (76/126 cases) and 39.7% men (50/126 cases). In most cases prophylaxis was initiated after occupational exposure (49.2%; 62/126 cases), followed by unprofessional exposure (42.9%; 54/126 cases) and prophylaxis of vertical transmission of HIV infection (7.9%; 10/126 cases). In 79.4% (100/126) of cases a CBV+LPV/r schema was used according to the institute guidelines and other prophylaxis schemes were used in 20.6% (26/126) of cases. Only 44.4% (56/126) of those exposed to potentially contaminated biologic products received prophylaxis for 28 days. In 54.8% of cases (69/126) prophylaxis duration was less than 28 days (1 day to 20 days) and in one case (0.8%) the duration of prophylaxis was over 28 days. The Matei Balș Institute applies the HIV prevention protocol for exposure to potentially contaminated biological products. This protocol applies to professional exposure (49.2%) and nonprofessional exposure (42.9%). The prophylaxis schedules used follow the recommendations of the local guide (CBV+LPV/r in 79.4% of cases) and the duration of prophylaxis is variable. These data indicate that there is a need to improve the knowledge of the measures to be taken in the event of accidental exposure to biological products from people with unknown/known HIV status. The effectiveness of antiretroviral therapy in 2017 in real life Elisabeta Otilia Benea 1 *, Liana Gavriliu 1, Daniela Camburu 1, Alina Cozma 1, Gina Ducu 1, Roxana Dumitriu 1, Mihaela Ionica 1, Manuela Podani 1, Șerban Benea 1 *oebenea@yahoo.com The introduction of antiretroviral (ARV) therapy has prolonged life expectancy as well as improving the quality of life in HIV-infected patients undergoing treatment. Monitoring of RNA-HIV levels and CD4 lymphocytes allows assessment of treatment efficiency and the development of measures to improve its quality. Retrospective analysis of the effectiveness of ARV therapy in patients from National Institute of Infectious Diseases Prof. Dr. Matei Balș, between 1 st of January and 30 th of June During the analyzed period the institute had 2604 HIV-infected persons. Of these 2372 received ARV treatment (91.1%). Men represented 61.6% (912/2372) and women 38.4% (912/2372). The median age of treatment subjects was 38.9 years (1-82 years). The persons in the age group have the highest share (54.4%; 1206 cases), followed by the age group years (35.8%; 794 cases), then by those over 60 years (7.2%; 159 cases) and those under the age of 20 (2.6%; 58 cases). 29.7% (704 cases) were in the first treatment regimen, 29.4% (698 cases) in the second regimen, 17.7% (419 cases) in the third regimen and 23.3% (551 cases) had more than 3 treatment regimens. 90.3% of patients (2143/2372 cases) receive 3 antiretroviral regimens; they used regimens with PIs (52.4%; 1123/2143 cases), with integrase inhibitors (20.6%; 441/2143 cases), with NNRTIs (18.7%; 401/2143 cases), with 3 NRTIs (2.8%, 60/2143 cases) and other three antiretroviral associations (5.5%; 118/2143 cases). Duting the analyzed period 2336 RNA-HIV tests and 3426 CD4 tests were performed. Analysis of RNA-HIV results shows that 75.6% of the patients had a load below 200 c/ml and 54.6% had a CD4 level above 500 cells/mmc. The main causes associated with an incomplete virological response were: initiation of treatment for less than 12 months, use of more than 3 antiretroviral regimens in history, repeated discontinuation of therapy, drug use and the use of PIs regimens. If 91.1% of the institute's patients receive ARV treatment, only 75.6% of them have RNA-HIV values below 200 c/ml with current treatment regimens. It analyzes the determinants and measures that could improve the effectiveness of antiretroviral therapy at the Prof Dr. Matei Balș Institute. Particular aspects of the immunological and virusological status of HBV in HIV seropositive patients Delia Adelina Vlad 1 *, Mariana Mărdărescu 1, Ana Maria Tudor 1,2, Ruxandra Neagu Drăghicenoiu 1, Alina Cibea 1, Dan Otelea 1, Dragoș Florea 1, Simona Paraschiv 1 8

9 2 Carol Davila University of Medicine and In Romania the rate of HBV infection in the HIVpositive population has registered an ascending trend. This trend refers both to vertically infected patients - maternal-fetal transmission and also to sexually infected people and injecting drug users. Management of HIV/HBV co-infections represents a public health issue in terms of therapeutic options In the Pediatric Immunosuppression Department in INBI Prof. Dr. Matei Balș, Bucharest we implemented a retrospective study on a sample of 73 HIV/HBV co-infected patients. The subjects were mainly HIV infected patients belonging to the Romanian cohorts, as well as later diagnosed cases. Data were processed from the medical charts for day and continuous hospitalization, as well as the electronic database of our institute, corroborating laboratory - biochemistry, immunology and molecular genetics data. We followed in dynamics the immunological and virological status for hepatitis B virus in HIVpositive patients under a specific treatment, and treatment resistance mutations in those with detectable viral loads. A total of 8.21% (6 of the 73) of HIV-HBV coinfected patients were in immunotolerance phase, 24.65% (18 of the 73) were in the active replication phase, 45.2% (33 of the 73) in the inactive phase, 5.47% (4 of the 73) were naturally cured, 16.43% (12 of the 73) were cured with treatment. Resistance mutations were detected in 15 patients, some of them with multiple mutations: 11 patients following lamivudine (73.33%), 10-entecavir (66.66%) and 8-telbivudine (53.33%). Resistance to tenofovir was not detected in any of the patients observed. The approach of HIV/HBV co-infection entails a close collaboration between the clinician and the laboratory physicians. Furthermore, the management of these patients represents a milestone due to the complexity of treatment, drug interactions and the existence of HBV virus resistance mutations. Evaluation of hematological parameters during direct acting antivirals and ribavirin regimen in HCV compensated cirrhotic patients Mariana Avricenco 1 *, Tiberiu Holban 2, Lilia Baba 1, Stela Cojocaru 2 *avricencomariana@gmail.com 1 Toma Ciorbă Clinical Hospital for Infectious Diseases, Chișinău, Republic of Moldova 2 State Medical and Pharmaceutical University Nicolae Testemiţanu, Chișinău, Republic of Moldova Since 2017 patients from Republic of Moldova with HCV compensated cirrhosis have access to direct acting antivirals (DAA) therapy. The regime includes the association of sofosbuvir +daclatasvir / ledipasvir with / without ribavirin. It is known that one of the effects of ribavirin therapy is anemia. Objective: we analyzed the hematological parameters disorders during treatment in HCV compensated cirrhotic patients treated in Clinical Hospital for Infectious Diseases Toma Ciorbă. The study involved patients with HCV genotype 1b Child Pugh A and B cirrhosis treated with ledipasvir / daclatasvir + sofosbuvir with ribavirin for 12 weeks. We studied the evolution of clinical and hematological, biochemical parameters and the viral load. The study included 20 patients with HCV cirrhosis: Child Pugh A 16 (80%) patients and Child Pugh B 4 (20%) patients. The mean age was 59.1 years. All patients initiated antiviral therapy with hemoglobin level more than 12 g/dl. At initiation of therapy, 12 (60%) patients had thrombocytopenia, from them: moderate thrombocytopenia had 7 (35%) patients and 5 patients severe (platelet count between /cmm and /cmm). At baseline, 14 (70%) patients had moderate leukopenia. After one month of treatment, the ribavirin was discontinued for 3 (15%) patients, and for 4 (20%) patients the dose was reduced. The reason for discontinuation of ribavirin was: for 1 patient the development of severe anemia (hemoglobin level 6 g/dl), 1 patient severe jaundice (total bilirubin more than 50 mg/dl), 1 patient cardiac disorders (tachycardia, severe asthenia, hypertension). At two months of therapy, the ribavirin dose was reduced for 5 (25%) patients who developed moderate anemia (hemoglobin values between 8.2 g/dl and 10 g/dl). Only 11 patients completed the full dose of ribavirin. At the end of therapy 6 patients improved their level of thrombocytes and 11 patients of 9

10 leukocytes. Only 4 patients remained with moderate thrombocytopenia and 2 patients severe (platelet count less than /cmm). After the completion of antiviral therapy, hemoglobin values were restored in all patients with anemia. All of the 20 patients after 12 weeks of treatment presented undetectable viral load. The most common adverse effect of antiviral therapy with ribavirin in the treatment of HCV infection is anemia. The efficacy of DAA therapy in compensated cirrhosis was not influenced by the dose reduction or discontinuation of ribavirin. The platelet count after the end of antiviral therapy was improved in all patients. Changes in liver fibrosis rates in HIV, HIV-HBV and HIV-HCV co-infected patients using APRI and Fib-4 indexes over a 10-year period Diana Gabriela Iacob 1 *, Catalin Tiliscan 1,2, Remulus Catana 1,2, Ioan Diaconu 1,2, Alexandra Dobrita 2, Carina Anca Mihalcut 1, Eliza Craciun 1, Anca Negru 1,2, Alina Orfanu 1,2, Cristina Popescu 1,2, Daniela Munteanu 1,2, Molagic Violeta 1,2, Raluca Nastase 1, Mihaela Radulescu 1,2, Simona Alexandra Iacob 1,2, Arama Victoria 1,2 *dianagiacob@gmail.com 2 Carol Davila University of Medicine and HIV co-infected patients with hepatitis C virus (HCV) and hepatitis B virus (HBV) progress more rapidly to liver fibrosis than HIV mono-infected patients. Considering the costs and the monitoring difficulties raised by these patients non-invasive biomarkers are needed to predict subsequent liverrelated complications. The current study assessed the use of Fib-4 index and aspartate to platelet index (APRI) to compare the progression of liver fibrosis between HIV and HIV co-infected patients with hepatitis C virus (HCV) and hepatitis B virus (HBV) in the past 10 years. We performed an observational retrospective study on 130 HIV infected patients, 40 HIV-HCV patients and 21 HIV-HBV cases. We used a cut-off values of 0.7 for the APRI and 1.45 for the Fib-4 score to delineate moderate liver fibrosis rates. Statistical analysis was performed using parametrical t-tests and non-parametrical tests (Kruskal Wallis and Mann Whitney), Pearson correlations and Kaplan Meier analysis, while considering p values below 0.05 as statistically significant. Median liver enzymes and APRI scores were significantly higher in HIV-HCV co-infected patients (p=0.023) compared with HIV monoinfected patients, despite the apparently small difference (-0.2 mean APRI difference, 95% CI [- 0.38, -0.29]). Furthermore HIV-HCV co-infected patients had a faster progression to liver fibrosis using both APRI and Fib-4 indexes (p=0.001, with a median 7 years until developing fibrosis). By comparison we recorded no other significant changes between APRI and Fib-4 values between the other studied populations. Overall, the most recent APRI and Fib-4 scores in all patients were associated with higher HIV RNA viral loads both at the most recent evaluation and 5 years prior (515 copies/ml, p=0.001 and 150 copies/ml respectively p=0.034) as well as with lower median CD4 counts in the past year and 5 years prior (288 cells/mm 3 p=0.004 and respectively 385 cell/mm 3, p=0.034), with no other correlations with previous HIV viral loads and CD4 counts. Interestingly, in this study the progression of liver fibrosis was not influenced by antiretroviral therapy or individual drug classes in any group. APRI and Fib-4 scores did not indicate any significant changes of liver fibrosis rates between HIV and HIV-HBV co-infected patients after 10 years. Instead HIV-HCV patients displayed a fast rate of progression to liver fibrosis. Overall, the changes of fibrosis scores over the past 5 years were correlated with higher plasma HIV RNA and lower CD4 counts, but not with antiretroviral therapy. Concordant and discordant between liver fibrosis evaluations using Fibroscan / Fibromax methods Iulian Diaconescu 1 *, Irina Niculescu 1, Mirela Ciucu 1, Andreea Mitroi 1, Daniela Culman 1, Manuela Musa 1, Anca Marian 1 *diaconescu_ig@yahoo.com 1 Victor Babeș Clinical Hospital of Infectious Diseases and Pneumology, Craiova, Romania The evaluation of liver fibrosis by non-invasive methods has been imposed lately to avoid the risk of liver biopsy. The sensitivity and specificity of the different methods differ and are not always consistent, so the authors recommend the correlation of these assessment rules. In this 10

11 presentation we aim to analyze the concordance and discordance between Fibroscan and Fibromax. The analysis included 20 patients who were evaluated with Fibroscan and Fibromax concomitantly. There were analyzed cases in which the two methods showed concordance (the same degree of fibrosis) or indicated different values. Of the 20 evaluations, Fibroscan could not be performed in 2 cases (10%) and the method could not be validated in 2 cases (10%). Fibrosis was evaluated conformable in 8 cases (50%). In 4 cases, Fibromax values were higher than those indicated by Fibroscan (25%). Discussions Hepatic fibrosis evaluations are crucial for access to the chronic hepatitis treatment. Using a single method there is the risk of depriving some patients of the recommended treatment of protocols. In the case of chronic hepatitis C, the concept of "abusive" treatment does not exist since all chronic hepatitis C benefit from antiviral treatment. As the current recommendations for access to therapy are limited by the degree of fibrosis, it can be discussed by a "discrimination" among patients evaluated by Fibromax alone. Fibroscan has the disadvantage that it cannot be done in all cases (20% of the patients could not be fibrous). In the evaluation of fibrosis of chronic viral hepatitis C, in case of values below F3 at Fibromax alternative methods of assessment (Fibroscan) would be required. The dynamic of APRI and FIB-4 scores in HCV cirrhotic patients after DAA therapy Anca Leuştean 1 *, Cristina Popescu 1,2, Alina-Elena Orfanu 1,2, Alexandra Badea 1, Codruţa Carp 1, Remulus Catană 1,2, Eliza Crăciun 1, Laurenţiu Stratan 1, Mihaela Rădulescu 1,2, Cătălin Tilişcan 1,2, Ioan Diaconu 1, Iulia Bodoşca 1, Diana Iacob 1, Violeta Molagic 1, Raluca Năstase 1, Sorin Ştefan Aramă 2, Victoria Aramă 1,2 *anca_leustean@yahoo.com 2 Carol Davila University of Medicine and Direct Acting Antivirals (DAA) have started being used in Romania since the end of 2015 for patients with HCV compensated cirrhosis, genotype 1. The National protocol stated that the liver fibrosis should be evaluated using Fibromax (BioPredictive) and patients with F4 at Fibrotest should be eligible for receiving treatment with ombitasvir, paritaprevir/ritonavir, dasabuvir and ribavirin. This prospective study conducted between November 2015 and August 2017 in the Third Department of Matei Balş National Institute for Infectious Disease evaluates the dynamic of other liver tests besides Fibromax in order to identify easier methods to evaluate the fibrosis for patients treated with DAA and who achieved SVR. The patients was evaluated at baseline and at 6 months post-end of treatment (post-eot) using Fibromax, AST to Platelet Ratio Index (APRI) and Fibrosis-4 score (FIB-4). In this study, 113 patients with HCV compensated cirrhosis received interferon-free treatment for 12 weeks. At baseline, according to Fibromax, 83.18% patients had F4, 6.19% had F3-F4, 8.84% had F3 and 1.76% had F2. Patients with lower scores at Fibrotest from the study met the clinical and biological criteria for liver cirrhosis and only 2 patients had F3 and severe depression and were excluded from the analysis. At treatment initiation, the mean value at Fibrotest for all 111 cirrhotic patients was 0.83±0.10; APRI: 1.50±1.25 and FIB- 4: 4.33±3.36. APRI and FIB-4 were correlated with the liver fibrosis graded by Fibrotest (r=0.224, p=0.03 for APRI and r=0.3, p=0.003 for FIB-4). These two scores were highly correlated (r=0.778, p<0.001). At 6 months post EOT, 82 patients were analyzed using APRI and FIB-4 and 54 of them with Fibrotest. The mean value for Fibrotest was 0.66±0.16, with a statistically significant difference between the two evaluations (95% confidence interval (CI) , p<0.001). The mean value for APRI at the second evaluation was 0.55±0.38, starting from a mean value of 1.55±1.11, also significantly decreased (95% CI , p<0.001). The mean value for FIB-4 at the 6 months evaluation was 2.60±1.70, starting from a mean value of 4.24±3.03. In this case, there is also a significant decrease (95% CI , p<0.001). The fibrosis in cirrhotic patients registered decrease at only 6 months since the end of treatment with Direct Acting Antivirals and APRI and FIB-4 prove to be easier non-invasive markers of liver stiffness, highly correlated at baseline with Fibrotest. Identification of phosphoinositide 3-kinases class II as a regulator for late stage of hepatitis C virus life cycle Ovidiu Vlaicu 1,2 *, Leontina Bănică 1, Simona Paraschiv 1, Dan Oţelea 1, Florin Pastrama 2, Cristian 11

12 Munteanu 2, Claire Gondeau 3, Charles-Henry Gattolliat 4, Tarik Asselah 4, Yves Rouilles 5, Jean Dubuisson 5, Costin-Ioan Popescu 2 *vlaicu.ovidiu@yahoo.com 2 Institute of Biochemistry of the Romanian Academy, Romania 3 INSERM U1183 Hepatic Stem cells, MSC and Biotherapies in liver Diseases Institute of Regenerative Medicine and Biotherapy (IRMB) Hospital Saint-Eloi, Montpellier, France 4 Department of Hepatology, Hôpital Beaujon, APHP, University Paris-Diderot and INSERM CRI UMR1149, Clichy, France 5 Hepatitis C Laboratory, Center for Infection and Immunity of Lille, University Lille Nord de France, CNRS-UMR8204, Inserm-U1019, Pasteur Institute of Lille, Lille, France Hepatitis C virus (HCV) infection evolves to chronicity inflicting liver disease ranging from steatosis and fibrosis to cirrhosis and hepatocellular carcinoma (HCC). Major progress has been recently achieved in HCV treatment with the emergence of direct acting antivirals (DAA). DAAs cure more than 90% of the patients infected with all HCV genotypes. However, the liver damage is not always reversible and HCC prognosis biomarkers are needed for patient treatment prioritization. HCV life cycle is deeply associated with lipid metabolism which may have a role in liver pathology. Thus, using molecular biology techniques associated with animal cell cultures and mass spectrometry analysis, we were able to identify different cellular, which may constitute future virus induced pathology biomarkers. We aimed to identify endogenous factors involved in both lipid metabolism and HCV life cycle identified by affinity purification (AP) followed by mass spectrometry analysis (Vlaicu et al., 2017). We constructed functional recombinant viruses with different foreign epitopes in HCV NS2 proteins suitable for AP. Further loss of function and gain of function assays were used to address the role of the endogenous factor in HCV life cycle. The gene expression was evaluated in primary hepatocytes (PHH) and patient liver biopsies with different fibrosis degrees. We identified class II phosphoinositide 3-kinase α (PI3KC2α) as an interactor of the NS2 complex in HCV producing cells. sipik3c2α downregulation showed that this isoform facilitates he entry and the replication steps and inhibits late stages of the HCV life cycle. We observed that PI3KC2α downregulation stimulated late stages of virion production (assembly, budding and secretion) in HCV cell culture. By intra and extracellular infectivity assays after brefeldin A treatment, we showed that both assembly and virion secretion steps were upregulated by isoform α downregulation. The phenotype rescue and mutant rescue assays showed that the N-terminal domain of the PI3KC2α is involved in virion production inhibition. Moreover, it was shown that the N- terminal domain of PI3KC2α might be required for its interaction with HCV NS2 complex. The viral infection did not significantly change the kinase expression neither in PHH or patient liver biopsies. PI3KC2α positively regulates the early stage (entry and replication) and inhibits late stage (assembly, secretion) of HCV life cycle strengthening the concept of endocytic pathway involvement in viral morphogenesis. Acknowledgement ERA-NET INFECT ERA HCV-ASSEMBLY 4007/2014. Lymphocytosis in patients with chronic viral hepatitis C the impact of antiviral therapy Gabriel Colțan 1 *, Tatiana Colțan 1, Cristina Marin 1, Mariana Gabriela Anghel 1, Adriana-Ionela Constantin 1, Mihai Olariu 1 *gabriel.coltan@gmail.com It is known that chronic viral hepatitis C may be accompanied by hematological changes such as lymphocytosis. Chronic viral hepatitis C is a risk factor for B cell non-hodgkin lymphoma. Of the hundreds of patients monitored over the years, we found 11 patients with lymphocytosis. We analyzed the group in terms of sex, age, background, HCV transmission pathway, HCV genotype, IL-28 B, monitoring period, associated disease, hematological evaluation (lymphocyte immunophenotyping ±medullary puncture), antiviral treatment. No patient experienced HIV coinfection. No patient developed malignant lymphoma. Peg interferon therapy + ribavirin or/ and DAA, followed by sustained virologic response, long time undetectable viremia did not influence the hematological aspect. 12

13 If hepatitis C virus is considered a lymphotropic virus, the replication cycle occurring in hepatocytes, lymphocytes, mononuclear cells, T and B lymphocytes, it is interesting to analyze that the hematological aspect does not change in cured patients. Late HBV reactivation in patients with rheumatic diseases treated with biological therapy Violeta Molagic 2 *, Cristina Popescu 1,2, Cristina Murariu 2, Catalin Tiliscan 1,2, Laurențiu Stratan 2, Raluca Nastase 2, Cristina Covaliov 2, Viorica Poghirc 2, Victoria Arama 1,2, Stefan Sorin Arama 1 *violeta_molagic@yahoo.com 1 Carol Davila University of Medicine and 2 National Institute for Infectious Diseases Prof. Hepatitis B virus (HBV) infection is still prevalent in Romania. HBV reactivation (HBV-R) is an important issue as to biological therapy has become more used for rheumatic diseases (RD). This study aimed to evaluate the HBV infection outcome in patients diagnosed with RD and HBV undergoing biological therapy. We performed a cross sectional study that include patients with RD treated with biological therapy and at least one serological marker for HBV infection. The patients were monitored in the 3 rd department of Prof. Dr. Matei Balș National Institute of Infectious Diseases, between Serum HBsAg, anti-hbc, anti-hbs, ALT and HBV-DNA was measured at baseline and at the moment of reactivation. We enrolled 39 HBV infected patients:18 cases (46%) male and 21 cases (54%) female with median age years. Most cases were rheumatoid polyarthritis (23 cases), ankylosing spondylitis (8 cases), psoriatic arthritis (5 cases), systemic lupus erythematosus (2 cases) and one Sjogren syndrome. Five patients were diagnosed with hepatitis B surface antigen-negative/antihepatitis B core IgG antibody-positive. One of them experienced hepatitis B surface antigen seroreversion and important hepatitis flare (ALT>30XULN) after 12 cycles of rituximab therapy but there were no associated clinical manifestations. Antiviral therapy with entecavir was started immediately after HBV-R and resulted in the control of HBV infection within a few months. HBV-R rate was 12.82% (5 cases: 2 patients during treatment with infliximab, two with rituximab and one with etanercept). None of this patients received prophylactic or preemptive antiviral therapy. Patients from this category were treated with lamivudine or entecavir after HBV-R and had a favorable outcome. No deaths caused by hepatic failure were registered. The risk of hepatitis B virus reactivation was 12% in RD patients receiving biological therapy. Even patients with negative HBs antigen can reactivate HBV infection during immunosuppression, requiring close monitoring. Clinical correlations of antibiotic resistance on bacterial isolates from urine cultures in Infectious Diseases Clinic Galați Manuela Arbune 1 *, Miruna-Luminita Draganescu 1, Alina Viorica Iancu 1, Iris Frumuzache 2, Gabriela Gurau 1 *manuela.arbune@ugal.ro 1 Dunărea de Jos University from Galați, Romania 2 Infectious Diseases Clinical Hospital Galați, Romania Urinary tract infection (UI) antibiotic treatment, either in hospital or community, is involved into the development and spread of microbial resistance. The retrospective study analyzed the urine bacterial isolates from adults admitted to Infectious Diseases Clinic Galați during Diagnosis of acute pyelonephritis, cystitis or asymptomatic bacteriuria is based on clinical and laboratory criteria. Demographics, clinical appearance, Charlson's comorbidities score and antibiotic resistance data were collected from the medical records. Statistical analyses used the Student t test or the Mann- Whitney U test for continuous variables and the χ 2 test for categorical variables, with significance level p<0.05. There are identified 125 urine bacterial isolates, specified as E. coli (64%) and Klebsiella spp. (36%). Demographic characteristics are average age 59.8 ± years old, predominance of female gender (96/29), urban area (79/46) and average score 4.87 ± 3.06 of Charlson comorbidities index. The traditional factors related to urinary infections (UI) are: urinary catheter (16%), pelvic tumors (15.2%), recent surgery (13.2%), 13

14 lithiasis (8.8%), urinary incontinence (8.8%), pregnancy (5.2% of women) and age over 65 (51.2%). The fever (52%), urinary syndrome (34.4%), lumbar pain (38.4%, vomiting/diarrhea (43.2%) and other symptoms (36.8%) are notified as clinical features. Diagnostics are classified as cystitis (20%), pyelonephritis (28%) and asymptomatic bacteriuria (52%). Antibiotic treatment is reported in 65.6% of patients, including 43% cases of asymptomatic bacteriuria. The first-line antibiotic treatment is concordant with bacterial sensitivity in 61%. The resistance profile evidenced 16% ESBL positive strains, 23.2% MDR, 24% XDR, 2.4% PDR. Klebsiella spp. is more frequently associated with pyelonephritis (p <0.001) and higher antibiotic resistance (p=0.003) than E. coli. The prediction of antibiotic multiple resistance should be estimated based on the correlations with recent antibiotic use (p=0.001), recent invasive procedures (p=0.008), urinary catheter (p=0.003), chronic kidney disease (p=0.007) and hemiplegia (p=0.019). Most urine isolates are associated with asymptomatic bacteriuria and are contributing to the misuse of antibiotics. The etiology of UI with Klebsiella spp. is increasing the risk of first-line inappropriate antibiotic therapy. The careful judgment selection of urine culture recommendation, accurate follow-up of processing the urine samples, and decision of using new drugs in the first line of treatment in patients with predictor conditions for the antibiotic resistance are counting for optimization antibiotic stewardship in UI. Phenotypes of staphylococcal resistance clinical and therapeutic implications in severe sepsis Claudia-Elena Plesca 1 *, Tudorita Gabriela Ungureanu 1, Maria Obreja 2, Carmen Doina Manciuc 1,2, Mihaela Catalina Luca 1,2, Isabela-Ioana Loghin 1,2, Egidia Gabriela Miftode 1,2 *claudia23badarau@yahoo.com 1 Gr.T.Popa University of Medicine and Pharmacy, Iași, Romania 2 Infectious Diseases Hospital Sf. Parascheva, Iași, Romania Staphylococcus aureus remains the main Grampositive germ with a major implication in the determinism of severe systemic infections, especially in the context of a high level of antibiotic resistance. The study included 169 patients who were diagnosed with severe sepsis and were hospitalized in the Infectious Diseases Hospital from Iași between January 2013-december A number of 52 patients presented positive blood cultures with Staphylococcus aureus. In the majority of the cases, the entrance gate of the infection was cutaneous and in some of the cases it was urinary, respiratory or digestive. The presence of central/peripheral catheters represented an additional risk factor for the septic process development. We found that more than 60% of staphylococcal isolated strains were methicillin resistant, even those community-acquired. Because of the inducible resistance a low number of MRSAstrains were simultaneously sensitive to macrolides and lincosamides, fitting in the phenotype MLSBc (22%). Seventy-seven percent of the oxa-sensitive staphylococci were also sensitive to aminoglycosides and only 8% of the oxa-resistant strains presented these characteristics. We have also noticed a low resistance level to trimethoprimsulfamethoxazole of both MRSA and MSSA staphylococci. The sensitivity of staphylococcal strains to glycopeptides and linezolid reached 100% for both categories of Gram-positive germs. s In the case of Staphylococcus aureus strains isolated from the blood cultures of patients diagnosed with severe sepsis, the most frequent phenotype was the methicillin-resistant one. The high percentage of MRSA strains with associated resistance to macrolides, lincosamides, aminoglycosides and tetracycline has a major impact on the therapeutic management of severe sepsis cases. Co-trimoxazole could become a saving option in some clinical situations, associated to at least one of the bactericidal antimicrobial agent, of course. Epidemiological and clinical aspects regarding resistance of bacterial agents involved in community-acquired sepsis Brindusa Tilea 1,2 *, Anca Lazar 1, Evelyn Both 1, Marta Rotaru 1, Simona Horhat 1, Andrei Bogdan 2 *brindusa_tilea@yahoo.com 1 Clinical County Hospital Mureș, Romania 2 University of Medicine and Pharmacy Tîrgu Mureș, Romania Sepsis has become a global health problem due to increasing pathogenic agent resistance, with high 14